The plasma protein profile and cardiovascular risk differ between intima-media thickness of the common carotid artery and the bulb: A meta-analysis and a longitudinal evaluation

Lars Lind, Bruna Gigante, Yan Borne, Anders Mälarstig, Johan Sundström, Johan Ärnlöv, Erik Ingelsson, Damiano Baldassarre, Elena Tremoli, Fabrizio Veglia, Anders Hamsten, Marju Orho-Melander, Jan Nilsson, Olle Melander, Gunnar Engström

Research output: Contribution to journalArticle

Abstract

Background and aims: Genetic loci associated with CHD show different relationships with intima-media thickness in the common carotid artery (IMT-CCA) and in the bulb (IMT-bulb). We evaluated if IMT-CCA and IMT-bulb differ also with respect to circulating protein profiles and risk of incident atherosclerotic disease. Methods: In three Swedish cohorts (MDC, IMPROVE, PIVUS, total n > 7000), IMT-CCA and IMT-bulb were assessed by ultrasound at baseline, and 86 cardiovascular-related proteins were analyzed. In the PIVUS study only, IMT-CCA and IMT-bulb were investigated in relation to incident atherosclerotic disease over 10 years of follow-up. Results: In a meta-analysis of the analysis performed separately in the cohorts, three proteins, matrix metalloproteinase-12 (MMP-12), hepatocyte growth factor (HGF) and N-terminal pro-B-type natriuretic peptide (NT-proBNP), were associated with IMT-CCA when adjusted for traditional cardiovascular risk factors. Five proteins were associated with IMT-bulb (MMP-12, growth/differentiation factor 15 (GDF-15), osteoprotegerin, growth hormone and renin). Following adjustment for cardiovascular risk factors, IMT-bulb was significantly more closely related to incident stroke or myocardial infarction (total number of cases, 111) than IMT-CCA in the PIVUS study (HR 1.51 for 1 SD, 95%CI 1.21–1.87, p < 0.001 vs HR 1.17, 95%CI 0.93–1.47, p = 0.16). MMP-12 levels were related to this combined end-point (HR 1.30, 95%CI 1.08–1.56, p = 0.0061). Conclusions: Elevated levels of MMP-12 were associated with both IMT-CCA and IMT-bulb, but other proteins were significantly related to IMT in only one of these locations. The finding that IMT-bulb was more closely related to incident atherosclerotic disease than IMT-CCA emphasizes a difference between these measurements of IMT.

Original languageEnglish
Pages (from-to)25-30
Number of pages6
JournalAtherosclerosis
Volume295
DOIs
Publication statusPublished - Feb 2020

Keywords

  • Atherosclerosis
  • Carotid artery
  • Meta-analysis
  • Proteomics
  • Ultrasound

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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    Lind, L., Gigante, B., Borne, Y., Mälarstig, A., Sundström, J., Ärnlöv, J., Ingelsson, E., Baldassarre, D., Tremoli, E., Veglia, F., Hamsten, A., Orho-Melander, M., Nilsson, J., Melander, O., & Engström, G. (2020). The plasma protein profile and cardiovascular risk differ between intima-media thickness of the common carotid artery and the bulb: A meta-analysis and a longitudinal evaluation. Atherosclerosis, 295, 25-30. https://doi.org/10.1016/j.atherosclerosis.2020.01.011